Application of the silicon-tether strategy for controlling the regioselectivity and diastereoselectivity of intramolecular nitrone cycloadditions foraminopolyol synthesis
T. Ishikawa et al., Application of the silicon-tether strategy for controlling the regioselectivity and diastereoselectivity of intramolecular nitrone cycloadditions foraminopolyol synthesis, J AM CHEM S, 122(32), 2000, pp. 7633-7637
Highly regioselective and diastereoselective intramolecular chiral nitrone
cycloaddition reactions with a vinyl group tethered by a silicon atom have
been developed as a general method for the synthesis of stereodefined amino
polyols. This strategy features a series of one-pot reactions involving (1
) DIBAH reduction of the carbonyl groups of chiral alpha- or -beta-hydroxy
carbonyl compounds, in which the hydroxy group is protected as diphenylviny
lsilyl ethers, at -78 degrees C to give an aldehyde, (2) condensation of th
e aldehyde with N-benzylhydroxylamine to furnish nitrone (-78 degrees C -->
rt), and (3) intramolecular [3 + 2] dipolar cycloaddition reaction between
the nitrone and the silicon-tethered vinyl group (rt --> 70 degrees C, 3-1
5 h) to give isoxazolidine derivatives as direct precursors for amino polyo
ls. Since the cycloaddition reaction is concerted in nature and passes thro
ugh a fused-bicyclic transition state, the substituents, the nitrone substr
ate, and the silicon atom bias the stereochemical course of this addition,
resulting in highly diastereoselective and synthetically useful transformat
ions.